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ABSTRACT Objective Methods Results Conclusion To evaluate long‐term infection rates in children aged 6 months to 5 years with moderate‐to‐severe atopic dermatitis (AD) treated with dupilumab.This was a post hoc analysis of an ongoing open‐label extension (OLE) study of dupilumab. Pediatric patients aged 6 months to 5 years with moderate‐to‐severe AD who had previously taken part in the LIBERTY AD PRESCHOOL phase 2 and 3 clinical trials received weight‐based subcutaneous dupilumab every 2 or 4 weeks. Exposure‐adjusted infection rates after a median dupilumab exposure of 52 weeks are compared with data from the earlier randomized, placebo‐controlled, 16‐week LIBERTY AD PRESCHOOL phase 3 trial.Infection rates were overall lower in the OLE study compared with the dupilumab and placebo groups in the earlier 16‐week trial, including total infections (101.0 patients/100 patient‐years [PY]), nonherpetic skin infections (22.7 patients/100PY), herpetic infections (7.3 patients/100PY), and nonskin infections (92.9 patients/100PY). The frequency of severe and serious infections was low (3.1 patients/100PY), compared with 17.1 placebo‐treated patients/100PY and 0 dupilumab‐treated patients in the earlier 16‐week trial, and no infections leading to treatment discontinuation were observed. Systemic anti‐infective medication use (58.9 patients/100PY) was lower in the OLE study compared with both the dupilumab and placebo groups in the 16‐week trial.Overall, reduced infection rates are observed in infants and young children with moderate‐to‐severe AD treated with dupilumab long‐term, supporting the known safety profile of dupilumab. [ABSTRACT FROM AUTHOR]

Patients with moderate-to-severe atopic dermatitis (AD) experience intense chronic itch and impaired sleep. Reports from parents and teachers suggest that AD patients may also have attention problems. However, attention has not yet been directly assessed in AD patients. We utilized an objective, computer-based continuous performance test (CPT) validated for use in attention-deficit/hyperactivity disorder (ADHD) diagnosis to formally evaluate attention in adolescent AD subjects. This was a single-visit, cross-sectional, non-interventional study of moderate-to-severe (Investigator’s Global Assessment [IGA] ≥ 3) AD subjects aged 12–17 years without clinician-diagnosed ADHD. Attention was evaluated using two performance-based measures: Conners, CPT-3 and the Stroop Color and Word Test. The primary parameter was CPT-3 detectability (d’) measure. Lesional severity measures included Eczema Area and Severity Index (EASI) and body surface area (BSA) involvement. Subjects completed self-report rating scales assessing sensory responsiveness patterns (Adult/Adolescent Sensory Profile [AASP]), itch (Peak Pruritus Numerical Rating Scale [PP-NRS]), skin pain, quality of life, sleep, anxiety, and depressive symptoms. A total of 44 subjects were included in the study (61.4% female; mean age 15.0 [SD 1.78] years; mean EASI 20.4 [SD 7.8]; mean PP-NRS 7.0 [SD 1.8]). Results indicated substantial disease impact on sleep, quality of life, and comorbid anxiety and depressive symptoms. The mean (SD) Conners, CPT-3 dʹ T-score was 48.7 (SD 10.7), similar to the expected mean from a randomly selected age/gender-matched sample of the general population (50 [SD 10], by definition). Overall, 13.6% of subjects exhibited a dʹ T-score ≥ 60 (clinically significant poor performance), which was not greater than the expected general population value (15.9%). Subject-level data review by two psychologists determined that only 2 subjects demonstrated an overall response pattern that clearly indicated attention deficit. Many subjects had atypical sensory responsiveness profiles: sensory hypersensitivity (38.6%), sensory avoidance (50%), and low registration (hypo-sensitivity, 36.4%). Adolescents with moderate-to-severe AD without existing ADHD diagnosis did not demonstrate greater attention problems on performance-based measures than would be expected in age/gender-matched peers. Trial registration NCT05203380.Plain Language Summary: Atopic dermatitis (often shortened to AD) is a long-term skin disease that causes intense itching. It affects patients’ lives in many ways, including interrupting their sleep. Parents and teachers of young people with AD have sometimes suggested that AD may also cause attention problems. But this has never been tested properly. We measured the attention of 44 adolescents aged between 12 and 17 years who all had moderate-to-severe AD. We used computerized tests of attention that were developed for young people with ADHD (attention deficit hyperactivity disorder). Also, we made sure that none of the 44 patients had also been diagnosed with ADHD. The severity and extent of the patients’ AD was measured by doctors. We also used some measures that allowed the patients to report how AD affected their lives, including things like itch, skin pain, quality of life, sleep, anxiety, and depression. The adolescent patients reported that AD had a negative effect on various areas of their lives, including sleep and quality of life, and that it resulted in anxiety and symptoms of depression. However, the results of the attention tests in adolescents with AD were similar to what would usually be expected in adolescents without AD. Only 2 of the 44 patients with AD were found to have clear evidence of attention problems. The study concluded that adolescents with moderate-to-severe AD did not have any greater attention problems than would usually be expected in adolescents without AD. [ABSTRACT FROM AUTHOR]

Background/purpose: Dystrophic epidermolysis bullosa (DEB), a rare genetic skin disease caused by loss-of-function mutations in COL7A1, the gene encoding type VII collagen (COL7), is characterized by skin blistering, scarring, and extracutaneous manifestations that markedly reduce patient quality-of-life. Beremagene geperpavec-svdt (‘B-VEC’) is a gene therapy employing a non-integrating, replicationdefective herpes simplex virus type 1 (HSV-1)-based vector encoding two copies of full-length human COL7A1 to restore COL7 protein after topical administration to DEB wounds. B-VEC was approved in the United States in 2023 as the first topical gene therapy and the first approved treatment for DEB. However, few providers have experience with use of this gene therapy. Methods: Data was obtained through literature review and the experience of providers who participated in the B-VEC clinical study or initiated treatment after B-VEC approval. Results: This review discusses the burden of disease, describes the clinical trial outcomes of B-VEC, and provides physician and patient/caregiver recommendations as a practical guide for the real-world use of B-VEC, which can be administered in-office or at the patient’s home. Conclusions: By continuing to optimize the practical aspects of B-VEC administration, the focus will continue to shift to patient-centric considerations and improved patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management. Objectives: The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE. Methods: In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg). Results: Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0–5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator's Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores. Conclusions: Consistent with results seen in adults, adolescents, and older children (aged 6–11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population. Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B). Plain Language Summary: Atopic dermatitis (AD) is a chronic inflammatory skin disease that often results in a high disease burden in young children and their families. Patients often need long-term treatment to control their disease symptoms, including itch and rash. Dupilumab treatment for 16 weeks has shown benefits in children aged 6 months to 5 years with moderate-to-severe AD, with an acceptable safety profile. As AD is likely to continue from childhood into adolescence and adulthood, there is a need for data supporting long-term use of dupilumab in young children. In this study, children who completed the 16-week study continued dupilumab treatment for up to 1 year, receiving 200 mg or 300 mg of dupilumab (depending on the child's bodyweight) every 4 weeks. Through the year of treatment, 78.2% of patients reported at least one side effect, most of which were mild or moderate. Only one patient interrupted treatment because of severe skin rash (hives), which was resolved in 1 day. At the end of the year, 36.2% of patients had clear or almost clear skin, and almost all (96.6%) achieved at least 50% improvement in their extent and severity of disease. Additionally, 79.3%, and 58.6% had at least 75% or 90% improvement in their extent and severity of disease. In summary, consistent with results seen in adults, adolescents, and older children, this study showed that 1-year dupilumab treatment provides continued benefits with an acceptable safety profile. These results support long-term continuous use of dupilumab in children aged 6 months to 5 years with moderate-to-severe AD. 5SqqskjZPmoHiNU8WnfbXp What is the long-term safety and efficacy profile in young children with moderate-to-severeatopic dermatitis treated with dupilumab? [ABSTRACT FROM AUTHOR]

Objective: Controlling molluscum contagiosum (MC) infections is critical in atopic dermatitis (AD) management. This post hoc analysis assessed the efficacy and safety of berdazimer gel, 10.3% (topical, antiviral, nitric oxide–releasing medication) versus vehicle in MC patients with or without AD. Methods: Three Phase 3, multicenter, randomized, double‐blind, vehicle‐controlled, parallel‐group trials (B‐SIMPLE[berdazimer sodium in molluscum patients with lesions]1, −2, −4) enrolled patients 6 months and older with 3–70 mollusca. Berdazimer or vehicle was applied once daily to all MC lesions for 12 weeks. Data from three Phase 3 studies were integrated for subgroup efficacy and safety assessments using several weighted meta‐analysis approaches. Patients with concurrent AD or a history of AD/eczema were categorized as AD+ subgroup (AD− when absent). Primary efficacy endpoint: complete lesion clearance at Week 12. Safety endpoints included adverse events (AEs) through Week 24 and local skin reactions through Week 12. Results: Of 1598 enrolled patients, 209 (13.1%) were AD+. Baseline mean lesion counts were greater in AD+ (26.4) than AD− (19.3). Complete clearance rates were higher at Week 12 for berdazimer compared with vehicle in AD+ (n = 209; 35.0% vs. 27.4%; odds ratio [OR], 1.3; 95% CI, 0.7–2.5) and AD− (n = 1389; 29.1% vs. 18.9%; OR 1.8; 95% CI 1.4–2.4) subgroups. AEs in AD+ were application‐site pain (21.6% with berdazimer vs. 11.9% with vehicle), dermatitis (12.8% vs. 2.4%), and erythema (9.6% vs. 7.1%). Conclusions: Berdazimer gel showed favorable efficacy regardless of AD status. Berdazimer‐induced erythema may be indistinguishable from AD symptoms or with inflammatory response upon resolution of molluscum. [ABSTRACT FROM AUTHOR]

Background: Patients with atopic dermatitis (AD), particularly infants and young children, are at greater risk of developing skin infections. In this study, we assessed infection rates in AD patients aged 6 months to 5 years treated with dupilumab. Methods: In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo, with concomitant low-potency topical corticosteroids, every 4 weeks for 16 weeks. Exposure-adjusted infection rates were used to compare treatment groups. Results: The analysis included 162 patients, of whom 83 received dupilumab and 79 received placebo. Total infection rates were not significantly different between the dupilumab and placebo groups (rate ratio [RR] 0.75, 95% CI 0.48–1.19; p = 0.223). Non-herpetic adjudicated skin infections and bacterial infections were significantly less frequent with dupilumab versus placebo (non-herpetic skin infections: RR 0.46, 95% CI 0.21–0.99; p = 0.047; bacterial infections: RR 0.09, 95% CI 0.01–0.67; p = 0.019), and the number of patients using systemic anti-infective medication was significantly lower in the dupilumab group (RR 0.52, 95% CI 0.30–0.89; p = 0.019). There were no significant differences in the number of herpetic infections between the dupilumab and placebo groups (RR 1.17, 95% CI 0.31–4.35; p = 0.817). The number of patients with two or more infection events was significantly higher in the placebo group (RR 0.29, 95% CI 0.12–0.68; p = 0.004), and no severe or serious infections (including eczema herpeticum) were observed among patients receiving dupilumab. Conclusions: These data suggest that dupilumab treatment in infants and children younger than 6 years with AD does not increase overall risk of infections and is associated with a reduced risk of bacterial and non-herpetic skin infections compared with placebo, resulting in a reduced need for anti-infective medication. Trial Registration: The trial was registered with ClinicalTrials.gov with ID number NCT03346434 on November 17, 2017. Infographic: Plain Language Summary: Patients with atopic dermatitis (AD), a chronic disease of the skin, are at greater risk of developing skin infections, particularly infants and young children. Several medications for AD may weaken the patient's immune system, further increasing the risk of infections. Dupilumab is a recently developed drug for AD that should not interfere with the patient's immune defenses against bacterial, viral, or fungal infections. In this study, we evaluated the effect of dupilumab on infections in children aged 6 months to 5 years with moderate-to-severe AD. Patients received 200 or 300 mg of dupilumab (depending on the child's weight) or placebo, together with ointments containing mild steroids, every 4 weeks for 16 weeks. At the end of treatment, total infections were not significantly different between patients receiving dupilumab and placebo. Furthermore, patients receiving dupilumab experienced significantly less bacterial and non-herpetic skin infections and used significantly less anti-infective medication compared with patients receiving placebo. Herpetic infections were also not significantly different between dupilumab- and placebo-treated patients. Finally, significantly more patients in the placebo group experienced two or more infections. This study demonstrates that dupilumab does not increase the risk of infections in infants and young children with AD and can decrease the use of anti-infective medication. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited treatment options for adolescents with moderate-to-severe disease. Lebrikizumab, a monoclonal antibody targeting interleukin (IL)-13, demonstrated clinical benefit in previous Phase 3 trials: ADvocate1 (NCT04146363), ADvocate2 (NCT04178967), and ADhere (NCT04250337). We report 52-week safety and efficacy outcomes from ADore (NCT04250350), a Phase 3, open-label study of lebrikizumab in adolescent patients with moderate-to-severe AD. The primary endpoint was to describe the proportion of patients who discontinued from study treatment because of adverse events (AEs) through the last treatment visit. Methods: Adolescent patients (N = 206) (≥ 12 to < 18 years old, weighing ≥ 40 kg) with moderate-to-severe AD received subcutaneous lebrikizumab 500 mg loading doses at baseline and Week 2, followed by 250 mg every 2 weeks (Q2W) thereafter. Safety was monitored using reported AEs, AEs leading to treatment discontinuation, vital signs, growth assessments, and laboratory testing. Efficacy analyses included Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Body Surface Area (BSA), (Children's) Dermatology Life Quality Index ((C)DLQI), and Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression. Results: 172 patients completed the treatment period. Low frequencies of SAEs (n = 5, 2.4%) and AEs leading to treatment discontinuation (n = 5, 2.4%) were reported. Overall, 134 patients (65%) reported at least one treatment-emergent AE (TEAE), most being mild or moderate in severity. In total, 62.6% achieved IGA (0,1) with ≥ 2-point improvement from baseline and 81.9% achieved EASI-75 by Week 52. The EASI mean percentage improvement from baseline to Week 52 was 86.0%. Mean BSA at baseline was 45.4%, decreasing to 8.4% by Week 52. Improvements in mean change from baseline (CFB) to Week 52 were observed in DLQI (baseline 12.3; CFB − 8.9), CDLQI (baseline 10.1; CFB − 6.5), PROMIS Anxiety (baseline 51.5; CFB − 6.3), and PROMIS Depression (baseline 49.3; CFB − 3.4) scores. Conclusions: Lebrikizumab 250 mg Q2W had a safety profile consistent with previous trials and significantly improved AD symptoms and quality of life, with meaningful responses at Week 16 increasing by Week 52. Trial registration: ClinicalTrials.gov identifier, NCT04250350. Plain Language Summary: Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis Atopic dermatitis is a chronic relapsing inflammatory skin disease that affects up to 15% of adolescents worldwide, with up to 50% suffering from moderate-to-severe disease. Signs and symptoms include dry, cracked skin; redness; itching; and painful lesions, which can negatively affect quality of life and lead to complications, including skin infections. Adolescents also report increased rates of anxiety and stress. Lebrikizumab is a novel monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, the key cytokine in atopic dermatitis, blocking the downstream effects of IL-13 with high potency. Lebrikizumab has been shown previously to improve symptoms of atopic dermatitis, including itch, skin clearance, and quality of life in ADvocate1, ADvocate2 and ADhere. The ADore study aimed to evaluate the safety and efficacy of lebrikizumab in adolescents with moderate-to-severe atopic dermatitis. Investigators recruited patients ≥ 12 to < 18 years old, weighing ≥ 40 kg, from Australia, Canada, Poland, and the US who were diagnosed with moderate-to-severe atopic dermatitis. These patients received a loading dose of 500 mg of lebrikizumab at Weeks 0 and 2, followed by 250 mg every 2 weeks for 52 weeks. The safety profile of lebrikizumab was consistent with previously published reports, with mostly mild or moderate adverse events, which did not lead to treatment discontinuation. Lebrikizumab improved skin clearance; 62.6% of patients had clear or almost clear skin by the end of the trial. Lebrikizumab also improved the patients' quality of life. These safety and efficacy results support lebrikizumab's role in treating adolescents with moderate-to-severe atopic dermatitis. D_n9HEaRPQDPZd1tfRjK-9 Safety and Efficacy of Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis: A 52-Week, Open-Label, Phase 3 Study (MP4 44681 KB) [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD)—a chronic inflammatory skin disease characterized by intense itching—can have a detrimental impact on quality of life (QoL). We report results of a quantitative assessment of pediatric patient, caregiver, and physician perceptions of AD burden in children and adolescents. Methods: Pediatric patients (aged 6–11 [children] or 12–17 [adolescents] years) with moderate-to-severe AD, their caregivers, and independent physicians were recruited in 13 countries. Caregivers and their children/adolescents completed an online survey about the impact of AD on 16 key items of patient QoL. Physicians completed surveys on their patients aged 6–11 and 12–17 years. Best–worst scaling was used to rank the importance of the QoL items. Results: Overall, 1447 children/adolescents with moderate-to-severe AD (aged 6–11 years: 701; 12–17 years: 746), 1447 caregivers, and 1092 physicians participated. Patients and caregivers in both age groups ranked disturbed sleep as the most important QoL item, followed by feeling ashamed because of AD. Independent physicians ranked feeling ashamed because of AD as the most important QoL item for both age groups, followed by disturbed sleep for those aged 6–11 years and being singled out for those aged 12–17 years. The relative importance of the 16 QoL items to patients was strongly aligned between patients in both age groups and their caregivers, but somewhat less so between patients and physicians. Between-country differences were more apparent in physician- versus patient-/caregiver-reported results. Conclusion: The most burdensome QoL items were impact of AD on sleep and feeling ashamed. Caregivers and physicians correctly identified the QoL items most burdensome to patients. However, patient and caregiver perceptions were generally more closely aligned than patient and physician perceptions. Between-country differences in perceptions (particularly for physicians) were observed, probably due to multifactorial reasons, necessitating further evaluation. 7cPtCLX2kauVz19PdNt3EW Video Abstract (MP4 42,877 kb) Infographic: [ABSTRACT FROM AUTHOR]

Introduction/Background While previous studies into continuous long-term dupilumab treatment for adults with moderate-to-severe atopic dermatitis (AD) demonstrated sustained efficacy, further study into long-term safety and efficacy data regarding dupilumab in children is needed. Objectives To evaluate the impact of treatment with dupilumab and low-potency topical corticosteroids (TCS) for up to 2 years on efficacy and safety measures in children aged 6 months to 5 years with moderate-to-severe AD. Methods Children aged 6 months to 5 years with moderate-to-severe AD, who had participated in prior dupilumab pediatric AD studies were enrolled in a phase 3 open label extension (OLE) study. Patients received subcutaneous dupilumab every 4 weeks; 200 mg for children weighing 5 to <15 kg, 300mg for 15 to <30 kg. Topical AD treatments were allowed. Efficacy outcomes assessed include the proportion of patients who achieved 75% improvement from baseline in Eczema Area and Severity Index (EASI-75) score and the proportion of patients who achieved an Investigator Global Assessment (IGA) score of 0/1 as observed from OLE baseline to 2 years. Safety was also evaluated. Results A total of 180 patients were included in the 6 month to 5 years cohort; mean (±SD) age at OLE baseline was 3.9 (1.3) years with mean (SD) duration of AD of 3.5 (1.3) years. At OLE baseline, 29.4% of patients achieved EASI-75, improving to 85.1% at 52 weeks and 92.1% at 104 weeks. Similarly, 12.8% of patients achieved IGA 0/1 at OLE baseline, improving to 36.0% at Week 52 and 40.6% at Week 104. Total treatment-emergent adverse events (TEAEs) were observed in 87.8% of patients (intensity: mild 24.4%, moderate 52.2%, severe 11.1%). TEAEs assessed as related to dupilumab by the study investigators were reported in 18.3% of patients; the most prevalent were conjunctivitis (2.8%), allergic conjunctivitis (1.7%), nasopharyngitis (1.7%) and urticaria (1.7%). Serious TEAEs assessed as related to dupilumab by the study investigators were observed in 0.6% of patients. Conclusions Treatment with dupilumab for up to 2 years in young children with moderate-to-severe AD demonstrated efficacy outcomes, with sustained improvement in clinical signs reported in a large proportion of patients. Results are consistent with the known safety profile for dupilumab. [ABSTRACT FROM AUTHOR]

Introduction/Background Children with moderate-to-severe atopic dermatitis (AD) are at increased risk of lower bone mineral density (BMD) and fractures. Peak bone mass achieved during prepubescence is a major determinant of lifetime risk of fractures and osteoporosis. Bone alkaline phosphatase (BALP) promotes bone mineralization and contributes to density and linear growth in children. Systemic corticosteroids (SCS) negatively impact growth and bone health. Objectives To describe the impact of dupilumab treatment on BALP in children aged 6–11 years with moderate-to-severe AD and prior history of SCS use. Methods BALP levels in sera from participants receiving dupilumab 300 mg every 4 weeks (q4w) or placebo in LIBERTY AD PEDS (NCT03345914) and dupilumab 300 mg q4w in LIBERTY AD PED-OLE (NCT02612454) were analyzed at baseline and at 8, 12, 16 (PEDS), and 52 weeks (PED-OLE). Serum BALP levels (mcg/L) were stratified by prior use (with SCS; n = 42) or with no prior use of SCS (without SCS; n = 203), as captured in PEDS patient history at baseline. Results Regardless of prior SCS use, dupilumab treatment led to significant increase in BALP levels in children with moderate-to-severe AD at Week 16 compared with the placebo group (with SCS: 300 mg q4w [n = 25] vs placebo [n = 17], mean change [standard deviation] in BALP levels of 15.1 mcg/L [16.5] vs −5.5 mcg/L [16.0], P = 0.0099; without SCS: 300 mg q4w [n = 97] vs placebo [n = 106], 11.8 mcg/L [18.8] vs 2.2 mcg/L [16.3], P = 0.0074). By Week 52, BALP levels further increased vs baseline regardless of prior SCS use and were comparable with reference intervals (with SCS: 24.5 mcg/L [16.8], P = 0.0044; without SCS: 13.4 mcg/L [19.4], P = 0.0002). Patients in the placebo group who switched to dupilumab in PED-OLE had improved to levels similar to those of patients continuing treatment by Week 52 (with SCS: 23.3 mcg/L [19.3], P = 0.0067 [vs baseline]; without SCS: 18.4 mcg/L [20.4], P < 0.0001 [vs baseline]). Conclusions Dupilumab treatment increased BALP levels in children aged 6-11 years with moderate-to-severe AD irrespective of prior history of SCS use. These results add to the body of evidence that moderate-to-severe AD can negatively impact BALP levels, and that this effect may be improved with dupilumab in this age group, regardless of history of SCS use. The increase in BALP levels suggests that dupilumab may help improve bone mineralization in children with moderate-to-severe AD when treated during prepubescence. [ABSTRACT FROM AUTHOR]

Background and Objective: Previous studies of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents, and severe atopic dermatitis in children aged 6 to < 12 years demonstrate no clinically important changes in laboratory parameters. The objective of this study was to assess laboratory outcomes in children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis treated with dupilumab. Methods: In this randomized, placebo-controlled, phase III trial of dupilumab, 161 children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis were enrolled from 31 sites in Europe and North America and randomized 1:1 to receive subcutaneous placebo or dupilumab (5 kg to < 15 kg: 200 mg; 15 kg to < 30 kg: 300 mg) every 4 weeks plus topical corticosteroids for 16 weeks. Hematology, serum chemistry, and urinalysis assessments were analyzed on blood and urine samples collected at screening and weeks 4 and 16; descriptive statistics are provided. Results: No clinically meaningful changes in laboratory parameters were observed. While two cases of eosinophilia and one case each of neutropenia and leukocytosis were reported as treatment-emergent adverse events in the dupilumab plus topical corticosteroids group, these events were not associated with clinical symptoms and did not lead to treatment discontinuation or study withdrawal. Conclusions: These results suggest that routine laboratory monitoring of children aged 6 months to < 6 years treated with dupilumab plus topical corticosteroids is not required. Limitations of this study include short study duration, and exclusion of patients with abnormalities in laboratory test results at screening. Clinical Trial Registration: ClinicalTrials.gov: NCT03346434, part B Plain Language Summary: Atopic dermatitis (AD) is a chronic, inflammatory skin disease that often causes itchy rashes. To reduce persistent AD signs and symptoms, patients may need to take medications that require laboratory monitoring. This can add to treatment burden, especially among infants and children. Dupilumab is a drug that specifically targets key molecules that underlie AD and has been tested in several clinical trials, now in patients 6 months and older. Studies in adults, adolescents, and children as young as 6 years of age with moderate-to-severe AD have shown that dupilumab can be used without the need for regular laboratory tests. In this study, the authors analyzed blood and urine samples collected during a clinical trial of dupilumab in 161 infants and children aged 6 months to 5 years with moderate-to-severe AD. Routine laboratory tests revealed no clinically meaningful changes in patients' blood and urine following treatment with dupilumab. In general, the laboratory results in these patients were similar to those in adults, adolescents, and children aged 6–11 years treated with dupilumab. Taken together, these findings suggest that dupilumab can be used for the continuous treatment of moderate-to-severe AD without the need for routine laboratory monitoring. [ABSTRACT FROM AUTHOR]

Introduction: Itch associated with atopic dermatitis (AD) has a profoundly negative effect on patients of all ages. Therefore, itch is a main target for AD therapeutic approaches, and treatments are perceived as beneficial when they achieve an itch reduction. In the absence of a validated scale for children aged 6–11 years that is suitable for assessing itch intensity in clinical trial settings, the Worst Itch Scale was developed. Methods: Qualitative interviews, comprising concept elicitation and cognitive debriefing, were conducted to develop and evaluate the content validity of the Worst Itch Scale. Psychometric assessments used data from the LIBERTY AD PEDS phase 3 trial of dupilumab in patients aged 6–11 years with severe AD. These included test–retest reliability, construct validity, known-groups validity and responsiveness. Thresholds for clinically meaningful change were defined using anchor- and distribution-based methods. Results: The Worst Itch Scale consisted of two items asking about 'worst itching' experienced 'last night' and 'today'. Worst Itch Scale scores showed large, positive correlations with existing patient-reported outcome (PRO) measures of itch, and weaker correlations with clinician-reported outcome (ClinRO) measures assessing objective signs of AD. Improvements in Worst Itch Scale scores were highly correlated with improvements in other itch PROs and moderately correlated with improvements in ClinROs. The responder definition based on the primary anchor, a 1-point improvement in the Patient Global Impression of Disease, was 2.84. Supportive anchors produced response estimates ranging from 2.43 to 4.80 points. Conclusions: The Worst Itch Scale is a fit-for-purpose (e.g. well-defined, reliable, responsive and valid) scale for evaluating worst itch intensity in children aged 6–11 years with severe AD. The within-patient threshold for defining a clinically meaningful response was a ≥ 3–4-point change in the Worst Itch Scale score. Trial Registration: NCT03345914. AJhHpBhQDRLsLFeB17Gfds Video: How can we reliably assess itch intensity in children 6-11 years with severe atopic dermatitis in clinical trial settings? [ABSTRACT FROM AUTHOR]

Background: Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis.Methods: This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to <15 kg: 200 mg; bodyweight ≥15 kg to <30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434.Findings: Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p<0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p<0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation.Interpretation: Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults.Funding: Sanofi and Regeneron Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: Standardized assessments for dystrophic epidermolysis bullosa (DEB) are needed. This prospective, multicenter, 4-week, observational study was designed to evaluate DEB assessments for suitability as clinical trial endpoints.Methods: Patients with confirmed DEB diagnosis and ≥ 5 measurable wounds were included. The primary outcome was change from baseline in wound surface area (WSA) of 5 selected wounds by 3-dimensional imaging. Secondary endpoints were change from baseline in clinician global assessment (CGA) of WSA, wound characteristics, disease-related questionnaires and instruments (disease severity, quality of life [QoL], pain and disability, and itch), and tolerability of procedures.Results: Of 30 enrolled patients, 29 completed the study (of whom, 28 had recessive DEB). Median age was 17.8 years (range, 3.8-58.7). All patients developed new or recurrent wounds during the 4-week study. Of the wounds selected at baseline, 45/150 (30.0%) healed by week 2; an additional 38 healed by week 4, while 8 of those healed at week 2 had recurred by week 4 for a total of 75/150 (50.0%) healed wounds at week 4. Mean values for WSA, CGA, and disease-related questionnaire and instrument scores remained steady during this 4-week observational study. Of the 10 disease-related questionnaires and instruments assessed, the scores for the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and the Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB) did not substantially overlap between moderate and severe disease. Between mild and moderate disease, only the EBDASI scores did not substantially overlap.Conclusions: These results stress the dynamic nature of wounds, even during a 4-week period of observation, and suggest that a combination of clinician-assessed outcomes and patient-/caregiver-reported outcomes is needed to provide a comprehensive assessment of DEB severity and impact. In addition, these results support the use of EBDASI and iscorEB to monitor disease severity as both produced scores that did not substantially overlap between disease severity strata. Clinical trial registration ClinicalTrials.gov, NCT02178969 . Registered 4 June 2014, https://clinicaltrials.gov/ct2/show/NCT02178969 . [ABSTRACT FROM AUTHOR]

Background/Objective: Patients with moderate‐to‐severe atopic dermatitis (AD) have increased risk of cutaneous and extracutaneous infections. Dupilumab has previously been associated with reduced risk of serious/severe infections and non‐herpetic skin infections in adults with moderate‐to‐severe AD. This analysis assessed infection rates with dupilumab versus placebo in pediatric patients with moderate‐to‐severe and severe AD participating in clinical trials. Methods: This is a pooled analysis from two 16‐week, randomized, placebo‐controlled, phase 3 clinical trials of dupilumab: monotherapy in adolescents aged 12–17 years with moderate‐to‐severe AD (LIBERTY AD ADOL, NCT03054428) and with concomitant topical corticosteroids in children aged 6–11 years with severe AD (LIBERTY AD PEDS, NCT03345914). Data were pooled according to treatment received: placebo/approved dupilumab doses/other studied dupilumab doses/all dupilumab doses. Exposure‐adjusted rates (patients with ≥1 event per 100 patient‐years [nP/100 PY]) were used to compare treatment groups. Results: Overall, 612 patients were included: 205 received placebo and 407 received dupilumab (261 received approved dupilumab doses and 146 received other studied dupilumab doses). Overall infection rates were numerically lower with dupilumab versus placebo (nP/100 PY: placebo, 227; approved dupilumab, 173; other dupilumab, 206; all dupilumab, 184). Total skin infections were numerically less frequent in all dupilumab‐treated groups versus placebo (nP/100 PY: placebo, 67; approved dupilumab, 30; other dupilumab, 46; all dupilumab, 36). Conclusions: These data suggest that dupilumab treatment in children and adolescents with AD does not increase infection risk overall and is associated with lower rates of skin infections compared with placebo. [ABSTRACT FROM AUTHOR]

The article focuses on patient-reported outcomes and the burden of disease in pediatric patients with psoriasis, presenting real-world data from EU5 and the U.S., highlighting the substantial negative impact of pediatric psoriasis on quality of life and the prevalence of psychosocial disorders, with a specific focus on disease severity, itching, and treatment satisfaction.

Introduction/Background Atopic dermatitis (AD) is an inflammatory skin disease associated with atopic comorbidities, including asthma, food allergy, hay fever, and allergic conjunctivitis. Tralokinumab, a high-affinity monoclonal antibody that specifically targets IL-13, is indicated for the treatment of moderate-to-severe AD. Objectives: To assess the impact of atopic comorbidities on the efficacy and safety of tralokinumab vs. placebo for moderateto-severe AD in patients age ≥12 years. Methods: This post-hoc analysis presents data from the adult trials ECZTRA 1 and 2 (NCT03131648 and NCT03160885 pooled; 300 mg tralokinumab every 2 weeks [Q2W] vs. placebo) and ECZTRA 3 (NCT03363854; 300 mg tralokinumab Q2W vs. placebo, both plus TCS as needed), and the ECZTRA 6 adolescent trial (NCT03526861; pooled 150 mg and 300 mg tralokinumab Q2W vs. placebo). Tralokinumab-treated patients received a loading dose. Proportion of patients achieving IGA 0/1 and EASI-75 at Week 16 according to patient-reported current or past atopic comorbidity are presented as observed regardless of rescue medication use; missing data were imputed as non-responders. Results: In total 2,223 patients were included across four trials. Among patients in ECZTRA 1 and 2, 50.5% reported history of asthma, 38.5% food allergy, 53.8% hay fever, and 33.5% allergic conjunctivitis, while 19.8% reported no atopic comorbidities and 79.3% reported ≥1 atopic comorbidity. Proportions of patients in ECZTRA 3 and 6 reporting history of atopic comorbidities were largely similar, although more adolescent patients reported food allergy. In all subgroups at Week 16, higher proportions of patients receiving tralokinumab vs. placebo achieved EASI-75. In ECZTRA 1 and 2, response rates among patients in each subgroup were asthma: 35.3% vs. 12.8%, food allergy: 33.2% vs. 14.7%, hay fever: 36.8% vs. 16.5%, allergic conjunctivitis: 34.8% vs. 12.7%, none: 34.6% vs. 20.5%; and ≥1 atopic comorbidity: 35.5% vs. 15.2% (P<0.05 for all). A similar pattern of response was observed in ECZTRA 3 and 6, and for IGA 0/1 across trials. EASI-75 response rates for tralokinumab-treated patients were consistent across patients with different numbers of atopic comorbidities. Safety across subgroups was consistent with the safety profile of tralokinumab observed overall in adults and adolescents. Conclusions: 16 weeks of tralokinumab treatment improved AD signs and symptoms in adult and adolescent patients with and without atopic comorbidities, regardless of type or number of atopic comorbidities. The safety profile of tralokinumab was consistent between patients with and without atopic comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: In phase III trials in adolescents and children with atopic dermatitis (AD), dupilumab significantly decreased global disease severity. However, the effects of dupilumab on the extent and signs of AD across different anatomical regions were not reported. Here we characterize the efficacy of dupilumab in improving the extent and signs of AD across four different anatomical regions in children and adolescents. Methods: A post hoc subset analysis was performed using data from two randomized, double-blind, placebo-controlled, international multicenter, phase III trials of dupilumab therapy in adolescents aged ≥ 12 to < 18 years with moderate-to-severe AD and children aged ≥ 6 to < 12 years with severe AD. Endpoints included mean percentage change in Eczema Area and Severity Index (EASI) signs (erythema, edema/papulation, excoriation, lichenification) and extent of AD (measured by percentage of body surface area [% BSA] involvement) from baseline to week 16 across four anatomical regions (head and neck, trunk, upper extremities, lower extremities). Results: Dupilumab improved both the extent and severity of AD signs across the four anatomical regions. Improvements were shown to be similar across the four anatomical regions for % BSA involvement and for reduction in EASI signs. Improvements in all signs were seen early, within the first 4 weeks of treatment, and were sustained through week 16, across all regions. Conclusions: In pediatric patients 6 years of age and older, treatment with dupilumab resulted in rapid and consistent improvement in the extent and signs of AD across all anatomical regions. ClinicalTrials.gov Identifiers: LIBERTY AD ADOL (NCT03054428) and LIBERTY AD PEDS (NCT03345914). F7z4wqLwbkncM47ga-bUpB Does dupilumab provide improvement in atopic dermatitis across all anatomical regions in children and adolescents? (MP4 48,385 kb) [ABSTRACT FROM AUTHOR]

Background: Previous studies of dupilumab in adolescents and adults with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful adverse changes in laboratory parameters. Objective: The aim of this study was to assess laboratory outcomes in children aged 6–11 years with severe AD in a randomized, placebo-controlled, phase III trial of dupilumab. Methods: Children aged 6–11 years with severe AD were randomized 1:1:1 to 16 weeks of dupilumab 300 mg every 4 weeks, 100 or 200 mg every 2 weeks, or matching placebo, all with concomitant topical corticosteroids (TCS). Blood samples were collected at baseline and Weeks 4, 8, and 16; urine samples were collected at baseline and Weeks 4 and 16. Results: Of 367 patients enrolled in the study, 362 were included in the safety analysis, 351 completed study treatment, and 4 withdrew due to treatment-emergent adverse events not related to laboratory abnormalities. Both dupilumab + TCS groups showed overall trends toward increases in mean blood levels of eosinophils and alkaline phosphatase, and decreases in mean blood levels of platelets, neutrophils, and lactate dehydrogenase levels, without corresponding mean changes in the placebo + TCS group. None of these changes were associated with symptoms or clinically meaningful adverse outcomes, and none led to treatment modification. No clinically significant changes or trends were observed for other measured laboratory parameters. Conclusion: There were no clinically meaningful adverse changes in routine laboratory parameters attributable to treatment with dupilumab + TCS. Changes in platelet counts and lactate dehydrogenase levels likely reflect reduced inflammation. These results confirm similar findings in adults and adolescents, and suggest that there is no need for routine laboratory monitoring of children aged 6–11 years treated with dupilumab + TCS for severe AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03345914. 4bTSAzFaRmrELnrwsHf1S6 Does treatment with dupilumab require routine laboratory monitoring in 6- to 11-year-old children with severe atopic dermatitis? (MP4 180482 kb) [ABSTRACT FROM AUTHOR]

Background: Dystrophic epidermolysis bullosa (DEB) describes a rare genetic blistering disorder characterized by fragile skin. This study aimed to classify the frequency, demographics, cost, and comorbidities associated with emergency department (ED) visits due to DEB. Methods: The Nationwide Emergency Department Sample (NEDS) was analyzed for pediatric (age <18) ED visits from 2015 to 2019. DEB was identified with ICD‐10‐CM code Q81.2. Weighted frequency, prevalence, and 95% confidence intervals (CIs) of comorbidities were determined among ED visits with and without a DEB diagnosis. Results: From 2015 to 2019, 53 (weighted 242) cases of DEB among 27,223,220 pediatric ED visits were captured. Patients with DEB were more likely to visit the ED in summer compared with those without a diagnosis of DEB (35.7% vs. 21.4%, P <.05). More than half of patients with DEB were admitted to the hospital (56.2%, 95% CI: 39.3–72.5, P <.001) versus only 3.4% (95% CI: 3.1–3.7) of other patients. For ED visits with a secondary DEB diagnosis, the top three primary diagnoses were fever, constipation, and bone marrow transplant aftercare. Patients with DEB had higher rates of hypertension, cellulitis, sepsis, acute and chronic kidney injury, esophageal obstruction, gastroesophageal reflux disease, cardiomyopathy, and anxiety, compared to patients without DEB (all P <.001). Conclusions: DEB is a complex blistering disorder with multisystemic manifestations. Patients with DEB have significantly higher admission rates and commonly present with infectious or gastrointestinal complications. Understanding the features of ED visits due to DEB can better prepare healthcare teams and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory immune-mediated skin disease that affects both adults and children. Increased understanding of its pathogenesis has led to the development of highly effective therapeutic solutions in the form of biological drugs for adult patients with severe forms of the disease. The unpredictability of the action of adult-approved drugs in pediatric populations limited their usage in these patients for several years. However, this scenario has been changing, particularly in the last decade, increasing our knowledge of the clinical efficacy and safety of these drugs in pediatric populations. The approval/extensions to approvals of several biological agents throughout the year 2020 makes it important to update the topic. Five biological agents (etanercept, adalimumab, ustekinumab, secukinumab, and ixekizumab) have been approved by the European Medicines Agency for the treatment of psoriasis in pediatric populations, and three of them (etanercept, ustekinumab, and ixekizumab) were also approved by the US FDA for the same purpose. In total, 17 clinical trials of several distinct targeted therapies (tumor necrosis factor, interleukin [IL]-17 and IL-23, and phosphodiesterase-4 inhibitors) are ongoing in pediatric patients and will certainly provide crucial data on the subject, which could ultimately improve the armamentarium we have to target psoriasis in this special population. [ABSTRACT FROM AUTHOR]

Background: Chronic wounds are a fundamental issue for patients with epidermolysis bullosa (EB). Herein, we assess the natural history of wound closure in patients with EB who were randomly assigned to the vehicle-control arm of the multicenter, randomized, double-blind, phase 3 ESSENCE (NCT02384460) trial.Methods: ESSENCE was designed to assess the efficacy and safety of a topical cream formulation of 6% allantoin (SD-101 6%) vs vehicle (SD-101 0%) in patients ≥1 month old who had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional) and a target wound 10-50 cm2 present for ≥21 days. Time to complete target wound closure and the proportion of patients with target wound closure over time were analyzed overall and by parameters including patient age and baseline body surface area index (BSAi) of total wound burden (< 5% and ≥ 5%). Changes in BSAi of lesional skin, pain, and itching were also assessed.Results: The vehicle-control arm included 87 patients. Mean (standard deviation [SD]) time to target wound closure within 3 months was 53.6 (28.6) days, with a range of 14 to 142 days. The proportion of patients with target wound closure increased over time from 7.1% at day 14 to 53.6% at month 3. Mean (SD) changes from baseline in BSAi of total wound burden and BSAi of lesional skin at month 3 were -2.3% (6.3) and -5.0% (13.5) of total body coverage, respectively. Reductions in pain and itching were observed at day 7 and maintained for 3 months. Faster healing times and a greater proportion of patients with wound closure were observed in patients aged 1 month to < 2 years; those with wounds < 30 days old, and in those with BSAi of total body wound burden < 5%.Conclusions: Treatment response observed in the vehicle-control arm of the ESSENCE study was unexpectedly high and may have been due to unforeseen benefits of vehicle or enhanced wound care provided by the clinical trial staff. These observations will help inform the study design of future trials in patients with EB.Trial Registration: ClinicalTrials.gov , NCT02384460 ; Date of registration: February 13, 2015; First participant enrollment: March 11, 2015. [ABSTRACT FROM AUTHOR]

Background: Epidermolysis bullosa (EB) is a rare genetic disorder that manifests as blistering and/or skin erosion. There is no approved treatment for EB; current standard of care consists of wound and pain management. SD-101 6% is a topical cream containing 6% allantoin that was developed for treating skin lesions in patients with EB. The aim of this phase 3, multicenter, randomized, double-blind, vehicle-controlled study was to assess the efficacy and safety of SD-101 6% cream versus vehicle (0% allantoin) on lesions in patients with EB.Methods: Eligible patients were ≥1 month old, had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional) and a target wound 10-50 cm2 in size that was present for ≥21 days. Patients were randomly assigned to SD-101 6% cream or vehicle, which was applied topically once a day to the entire body for 3 months. Primary efficacy endpoints were time to complete target wound closure within 3 months and the proportion of patients who experienced complete target wound closure within 3 months. Post hoc subgroup analyses were conducted by patient age and in those with body surface area index of total body wound burden ≥5% at baseline.Results: In total, 169 patients were enrolled and randomly assigned to SD-101 6% (n = 82) or vehicle (n = 87). Baseline demographics and disease characteristics were similar between treatment groups. There were no statistically significant differences between treatment groups in time to target wound closure (hazard ratio, 1.004; 95% confidence interval [CI] 0.651, 1.549; P = 0.985) or proportion of patients with complete target wound closure within 3 months (odds ratio [95% CI], 0.733 [0.365, 1.474]; nominal P = 0.390). A positive trend toward faster wound closure with SD-101 6% versus vehicle was observed in patients aged 2 to <12 years and those with total body wound burden ≥5% at baseline. SD-101 6% cream was well tolerated.Conclusions: SD-101 6% cream for treatment of EB-associated lesions was not more effective than vehicle in shortening the time to complete target wound closure or achieving complete target wound closure within 3 months.Trial Registration: ClinicalTrials.gov, NCT02384460; Date of trial registration, February 13, 2015; First participant enrolled, March 11, 2015. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator's Global Assessment 0/1 at week 16. Objective: The objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of life. Methods: R668-AD-1526 LIBERTY AD ADOL was a randomized, double-blinded, parallel-group, phase III clinical trial. Two hundred and fifty-one adolescents with moderate-to-severe atopic dermatitis received dupilumab 300 mg every 4 weeks (q4w; n = 84), dupilumab 200 or 300 mg every 2 weeks (q2w; n = 82), or placebo (n = 85). A post-hoc subgroup analysis was performed on 214 patients with Investigator's Global Assessment > 1 at week 16. Measures of atopic dermatitis signs, symptoms, and quality of life were assessed. Clinically meaningful improvement in one or more of three domains of signs, symptoms, and quality of life was defined as an improvement of ≥ 50% in Eczema Area and Severity Index, ≥ 3 points in Peak Pruritus Numerical Rating Scale, or ≥ 6 points in the Children's Dermatology Life Quality Index from baseline. Results: Of patients receiving dupilumab q2w, 80.5% [66/82] experienced clinically meaningful improvements in atopic dermatitis signs, symptoms, or quality of life at week 16 (vs. placebo, 20/85 [23.5%], difference 57.0% [95% confidence interval 44.5–69.4]; q4w vs. placebo, 53/84 [63.1%], difference 39.6% [95% confidence interval 25.9–53.3]; both p < 0.0001). Results were similar in adolescents with Investigator's Global Assessment > 1 at week 16 (q2w, 46/62 [74.2%] vs. placebo, 18/83 [21.7%], difference 52.5% [95% confidence interval 38.5–66.6]; q4w, 38/69 [55.1%] vs. placebo, difference 33.4% [95% confidence interval 18.7–48.1]; both p < 0.0001). Conclusions: Dupilumab provided clinically meaningful improvements in signs, symptoms, and quality of life in adolescents with moderate-to-severe atopic dermatitis among patients with Investigator's Global Assessment > 1 at week 16. Treatment responses should be interpreted in the context of such clinically relevant patient-reported outcome measures. Trial Registration: ClinicalTrials.gov; NCT03054428. Adolescents with atopic dermatitis: does dupilumab improve their signs, symptoms, and quality of life? (MP4 212916 kb) [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic systemic inflammatory disease requiring long-term management. However, availability of long-term AD treatments with an acceptable risk-benefit profile is limited in pediatric patients. This ongoing phase 3 open-label extension (OLE; NCT02612454) enrolled patients aged 6 months to 17 years with moderate-to-severe AD. Patients were treated with dupilumab (weight-based dosing): 200 mg every 4 weeks (q4w; 5–14 kg), 300 mg q4w (15–29 kg) and 200 mg q2w (30–59 kg). Here we report safety data (cutoff date July 31, 2021) for 180 patients aged 6 months to 5 years who enrolled in the OLE. Of the 180 patients reported, 122 (67.8%) completed up to 16 weeks of the study, 30 (16.7%) up to Week 52 and 15 (8.3%) up to Week 156. A total of 167 (92.8%) patients were continuing treatment at the time of data cutoff. At baseline, the mean (SD) age was 3.9 (1.3) years. One hundred and nine (60.6%) patients reported treatment-emergent adverse events (TEAEs); the most common were nasopharyngitis (12.8%), upper respiratory tract infection (11.7%) and pyrexia (11.7%). One (0.6%) patient had a treatment-related severe TEAE (urticaria) that led to study drug discontinuation. Two (1.1%) patients had serious TEAEs (anaphylactic reaction and pneumonia mycoplasmal) of severe and moderate intensity, respectively. Both serious TEAEs were unrelated to treatment. Long-term safety of dupilumab in this pediatric population was generally consistent with the known dupilumab safety profile in adults and older pediatric patients. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous morphology and intense pruritus. Previous clinical trials have demonstrated that upadacitinib (UPA) was superior to placebo (PBO) in the treatment of moderate-to-severe AD. Here, we analyse the efficacy and safety of UPA across 52 weeks in adolescent and adult subgroups from three phase 3 studies. Patients were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30) or PBO orally once daily, either alone or with concomitant topical corticosteroids. After 16 weeks, patients in the PBO group were randomized to the UPA15 or UPA30 groups. For both adolescent and adult subgroups at 52 weeks, the proportion of responders in the UPA15 and UPA30 groups was: ≥70% and 83% for EASI75, ≥31% and 47% for vIGA-AD 0/1 and ≥37% and 61% for Worst Pruritus Numeric Rating Scale improvement ≥4. Children's Dermatology Life Quality Index (CDLQI) 0/1 was achieved by ≥15% (UPA15) and ≥28% (UPA30) of adolescents aged 12 to <16 years; DLQI 0/1 was achieved by ≥18% (UPA15) and ≥38% (UPA30) of adolescents aged 16 to <18 years and ≥30% (UPA15) and ≥45% (UPA30) of adults. Hospital Anxiety and Depression Scale (HADS-A and HADS-D) <8 was achieved in ≥28% of adolescents and ≥45% of adults for both treatment groups. Rates of serious adverse events (AEs) and serious AEs leading to discontinuation at week 52 were similar for both adolescents and adults. UPA15 and UPA30 responses in moderate-to-severe AD across 52 weeks were similar between adolescents and adults, with acceptable safety outcomes in both populations. [ABSTRACT FROM AUTHOR]

Abrocitinib is an oral, once-daily, Janus kinase 1–selective inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD). Recently, the US Food and Drug Administration expanded the indication of abrocitinib in adolescent patients with moderate-to-severe AD aged 12 to <18 years. Abrocitinib was efficacious and well tolerated in adolescent patients exposed for approximately 1 year of treatment in the JADE clinical program. This study aims to describe the updated long-term integrated safety profile of abrocitinib in adolescent patients treated in the JADE clinical program. This interim integrated safety analysis assessed data from patients aged 12 to <18 years who participated in the phase 3 JADE clinical trials MONO-1 (NCT03349060), MONO-2 (NCT03575871), TEEN (NCT03796676) and REGIMEN (NCT03627767) and subsequently enrolled in the ongoing phase 3 extension trial JADE EXTEND (NCT03422822; data cutoff: September 25, 2021). Data were pooled in two cohorts. The consistent-dose cohort comprised patients who received the same abrocitinib dose (200 or 100 mg) during the entire exposure time in the qualifying JADE trials, MONO-1, MONO-2 and TEEN and/or in JADE EXTEND. This cohort also included patients who did not meet the inclusion criteria for the maintenance period of JADE REGIMEN after abrocitinib 200 mg induction in the open-label period and subsequently received abrocitinib 200 mg in JADE EXTEND. The variable-dose cohort included patients who were randomly assigned to the maintenance period of JADE REGIMEN after induction and, hence, received different abrocitinib doses throughout exposure time in JADE REGIMEN, and subsequently entered in JADE EXTEND. Incidence rates (IRs) along with 95% CIs are presented as numbers of patients with events per 100 patient-years (PY). The analysis included 635 adolescent patients (exposure: 1011.4 PY). The consistent-dose cohort comprised 490 adolescents (730.6 PY): 289 received abrocitinib 200 mg (424.5 PY) and 201 received abrocitinib 100 mg (306.1 PY). Duration of exposure was ≥96 weeks in 38% and 37%, and ≥144 weeks in 8% and 4% of patients who received abrocitinib 200 or 100 mg, respectively. In the 200- and 100-mg arms, adverse events (AEs) occurred in 243 (84%) and 153 (76%) patients; 8% (IR [95% CI], 5.87 [3.76–8.74]) and 9% (5.87 [3.48–9.27]) experienced severe AEs and 10% (6.96 [4.69–9.93]) and 8% (5.13 [2.93–8.33]) discontinued the study due to AEs, respectively. The IRs of AEs of special interest were 1.84 (95% CI, 0.79–3.62) and 1.28 (0.35–3.27) for serious infection, 2.11 (0.97–4.01) and 1.62 (0.53–3.77) for all herpes zoster infections, and 0.69 (0.14–2.03) and 0.32 (0.01–1.77) for opportunistic herpes zoster infections in the 200- and 100-mg arms, respectively. One patient (aged 16 years) in the 200-mg arm had a nonfatal venous thromboembolism (VTE) event (pulmonary embolism; IR, 0.23 [95% CI, 0.01–1.28]); patient had a family history of pulmonary embolism. The variable-dose cohort comprised 145 adolescents (exposure: 280.8 PY). Adverse events occurred in 139 patients (96%) exposed to either abrocitinib dose; 10% (IR [95% CI], 5.15 [2.81–8.64]) had severe AEs and 11% (5.66 [3.23–9.19]) discontinued the study due to AEs. The IRs of AEs of special interest were 1.05 (95% CI, 0.22–3.07) for serious infection, 2.17 (0.80–4.72) for all herpes zoster infections and 0.35 (0.01–1.96) for opportunistic herpes zoster infections; no patients had VTE in the variable-dose cohort. In both the consistent-dose and variable-dose cohorts, there were no events of nonmelanoma skin cancer or other malignancies, tuberculosis or other opportunistic infections (excluding herpes zoster), major adverse cardiovascular events or deaths. In this integrated safety analysis using the most recent data cut from the ongoing JADE EXTEND trial, abrocitinib had an acceptable long-term safety profile in adolescents with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Background/Objective: Compared with the adult psoriasis population, knowledge about the incidence of comorbidities in the pediatric psoriasis population is limited. The objective of this study was to assess the prevalence and incidence of comorbidities, including psychiatric comorbidities, in patients with pediatric psoriasis. Methods: In this claims‐based, retrospective cohort study, patients with pediatric psoriasis were matched 1:3 with a nonpsoriasis cohort based on age, sex, and index date (the earliest of inpatient claims or the latter of two outpatient claims). Results: Obesity, serious infection, and juvenile idiopathic arthropathy had higher prevalence and incidence rates in the psoriasis cohort than the nonpsoriasis cohort. Psychiatric comorbidities were also more common in the psoriasis cohort than the nonpsoriasis cohort, as were ulcerative colitis and Crohn disease. Stratifying the psoriasis cohort by disease severity—mild and moderate‐to‐severe—found no differences in incidence rates of comorbidities between the two subsets. Conclusion: The incidence rates of many comorbid conditions were higher for patients with pediatric psoriasis compared with patients without pediatric psoriasis, and similar between patients with moderate‐to‐severe and mild pediatric psoriasis. [ABSTRACT FROM AUTHOR]

The progressive growth in nanotechnology approaches to diagnostics and therapeutics, especially for cancer, necessitates training physicians in nanoethics. This article explains why it is critical for medical education to include instruction in nanotechnology, nanomedicine, nanotoxicology, and nanoethics and suggests basic concepts educators can use to infuse curricula with this content. [ABSTRACT FROM AUTHOR]

Introduction: The impact of crisaborole ointment, a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD), on quality of life (QoL) was assessed in two identically designed phase 3 studies (AD-301: NCT02118766; AD-302: NCT02118792, both at http://www.clinicaltrials.gov).Methods: In both studies, patients aged ≥ 2 years with mild to moderate AD per the Investigator’s Static Global Assessment were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. QoL was assessed using the Children’s Dermatology Life Quality Index (CDLQI) (2-15 years), the Dermatology Life Quality Index (DLQI) (≥ 16 years), and the Dermatitis Family Impact Questionnaire (DFI) (parents/caregivers/family of patients aged 2-17 years). Established QoL score severity bands provided clinical context.Results: Greater mean improvement in QoL was observed in crisaborole-treated patients than in vehicle-treated patients at day 29 [mean change from baseline (∆BL), CDLQI: − 4.6 vs. − 3.0; P < 0.001; DLQI: − 5.2 vs. − 3.5; P = 0.015]. At baseline, more than half the patients had a “moderate effect” or higher of AD on QoL. At day 29, there was a trend toward more crisaborole- than vehicle-treated patients having “small effect” to “no effect”, The QoL of parents/caregivers/family improved more for crisaborole-treated than for vehicle-treated patients (∆BL, DFI: − 3.7 vs. − 2.7; P = 0.003).Conclusion: Crisaborole treatment results in clinically meaningful improvement in QoL for patients and their parents/caregivers/families.Trial Registration: AD-301: http://www.clinicaltrials.gov, NCT02118766; AD-302: http://www.clinicaltrials.gov, NCT02118792.Funding: Anacor Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., New York, NY. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis. Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis. Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16. Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes. Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52. Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018). Plain Language Summary: Atopic dermatitis, or eczema, is a condition that causes painful itchy dry skin, which is burdensome for patients and has a negative impact on quality of life. These symptoms frequently lead to disruption of daily activities such as school and work, decreased self-confidence, social isolation, anxiety, depression, and sleep disturbance. Symptoms of atopic dermatitis, such as itch and sleep disturbance, can only be assessed by patients. Therefore, it is important to consider patients' perceptions of their symptoms and the related impact on their quality of life, especially when evaluating treatment benefits. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. In two clinical trials (Measure Up 1 and Measure Up 2), we investigated how treatment with upadacitinib (15-mg or 30-mg dose) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis would impact their symptoms and quality of life over a 1-year period. We measured changes over time in patients' assessments of itch, pain, other skin-related symptoms, sleep, daily activities, emotional state, mental health, and overall quality of life. Patients treated with upadacitinib experienced improvements in symptoms of atopic dermatitis and quality of life within the first 1–2 weeks of treatment. These improvements continued to steadily increase in the following weeks and lasted through 1 year of treatment. In conclusion, once-daily treatment with upadacitinib 15 or 30 mg led to early and lasting improvements in the well-being of patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Children with atopic dermatitis (AD) are at risk for low bone mineral density (BMD), which is associated with an increased prevalence of osteopenia, osteoporosis, and fracture risk.1,2 Factors such as restricted nutrition, vitamin D deficiency, poor sleep and corticosteroid use contribute to lower bone alkaline phosphatase (BALP) levels, a marker of bone mineralization, seen in children with moderate-to-severe AD compared with healthy children.³ A major determinant for the lifetime risk of fractures and osteoporosis is the magnitude of peak bone mass achieved during prepubescent years. Low BALP and BMD in children with moderate-to-severe AD could contribute to a higher prevalence of osteopenia and osteoporosis. The objective of this analysis is to report the impact of dupilumab treatment on markers of bone formation in children aged ≥ 6 to <12 years with moderate-to-severe AD. The analysis was performed retrospectively on sera from participants in LIBERTY AD PEDS (NCT03345914) and LIBERTY AD PED-OLE (NCT02612454). In LIBERTY AD PEDS, a double-blind, 16-week, phase 3 trial, children aged 6 to <12 years were randomized 1 : 1 : 1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w for patients with baseline weight <30 kg, and 200 mg q2w for those with baseline weight ≥30 kg), or placebo; with concomitant medium-potency topical corticosteroids (TCS). After the initial 16-week trial, children aged 6 to <12 years were enrolled in the open-label extension study LIBERTY AD PED-OLE. Patients received dupilumab 300 mg q4w, which could be titrated up in case of inadequate clinical response at week 16 (200 mg q2w for patients with baseline weight <60 kg, and 300 mg q2w for those with baseline weight ≥60 kg); with concomitant medium-potency TCS. Bone biomarkers including BALP, procollagen type 1 N-terminal propeptide, C-terminal crosslinking telopeptide of type 1 collagen, osteocalcin, and insulin-like growth factor 1 were analysed at baseline, 8, 12, 16 and BALP only at 52 weeks. Dupilumab treatment led to a rapid and significant increase in geometric mean (standard error) levels of BALP in children with moderate-to-severe AD at 16 weeks compared with patients in the placebo group (77.7(1.02) μgL−1 vs. 65.0(1.04) μgL−1; P<0.0001). As well as a rapid and significant increase in BALP levels in children from the placebo group once they joined the OLE trial. BALP levels increased over 52 weeks in all treated children, reaching a level of 78–84 μgL−1 which constitutes a significant improvement compared with baseline, and is comparable to healthy reference intervals. An increasing trend from baseline to 16 weeks of dupilumab treatment was observed for other biomarkers, however, there was a limited number of data points due to insufficient volumes of serum available for analysis. These placebo-controlled results show, for the first time, a rapid and significant increase in BALP, and a possible trend in other biomarkers, in children with AD during treatment with dupilumab. These results suggest increased bone mineralization during the treatment period. [ABSTRACT FROM AUTHOR]

Many systemic therapies used for moderate-to-severe atopic dermatitis (AD) have immunosuppressive properties and necessitate laboratory screening and monitoring, adding to the treatment burden. Previous dupilumab studies in adults, adolescents and children aged 6–11 years with moderate-to-severe AD showed no clinically meaningful adverse changes in laboratory parameters. Here we evaluate hematology and chemistry laboratory safety data for dupilumab-treated children aged 6 months to 5 years with moderate-to-severe atopic dermatitis. Patients aged 6 months to 5 years with inadequately controlled moderate-to-severe AD were enrolled in LIBERTY AD PRESCHOOL (NCT03346434 part B), a randomized, double-blind placebo-controlled phase 3 study. 162 patients were randomized to either dupilumab 200/300 mg every 4 weeks (q4w; N=83; baseline weight ≥5 <15 kg: 200 mg; ≥15 to <30 kg: 300 mg) or placebo (N=79) for 16 weeks. From Day –14, all patients initiated standardized treatment with low-potency topical corticosteroids. Laboratory data was collected at baseline, weeks 4 and 16. At baseline, mean (SD) counts of hematology parameters were similar in both treatment groups: haemoglobin (dupilumab: 129.4 gL−1 [12]; placebo: 127.2 gL−1 [11.4]), lymphocyte (dupilumab: 4.6×109 L−1 [1.8]; placebo: 4.5×109 L−1 [1.7]), basophil (dupilumab: 0.07×109 L−1 [0.03]; placebo: 0.07×109 L−1 [0.04]), platelet (dupilumab: 397.7×109 L−1 [103.2]; placebo: 385.6 × 109 L−1 [112.9]) and eosinophils (dupilumab: 1.1×109 L−1 [0.7]; placebo: 1.1×109 L−1 [0.7]). Mean (SD) haemoglobin count in the dupilumab (128.4×gL−1 [11]) and placebo groups (128.2×gL−1 [11.2]), lymphocyte count in the dupilumab (4.20×109 L−1 [2.06]) and placebo groups (4.29×109 L−1 [1.52]) and basophil count in the dupilumab (0.07×109 L−1 [0.04]) and placebo groups (0.06×109 L−1 [0.03]) remained with the normal reference range for this population at week 16. The mean change (SD) in platelet count at week 16 was −16.3×109 L−1 (78.5) in the dupilumab group and +17.4×109 L−1 (106.6) in the placebo group. In the dupilumab treatment group, the mean eosinophil count increased at week 4 (mean change from baseline [SD]; +0.48×109 L−1 [1.8]) and trended downward by week 16 (+0.31×109 L−1 [1.4]) while minimal changes were noted in the placebo group at week 4 (0.1×109 L−1 [0.7]) and week 16 (−0.2×109 L−1 [0.7]). The values for creatine kinase, alkaline phosphatase, lactate dehydrogenase, blood urea nitrogen, albumin and protein at week 16 remained within the normal reference range in all treatment groups. Two patients in the dupilumab 200/300 mg q4w arm of this study reported treatment-emergent adverse events of severe and moderate eosinophilia. Neither event was associated with clinical symptoms nor led to the discontinuation of the study treatment. No clinically meaningful changes in hematology and chemistry parameters in children aged 6 months to 5 years with moderate-to-severe AD were seen with 16 weeks of dupilumab treatment. These data demonstrate that, as with adults, adolescents and older children, routine laboratory monitoring is unnecessary in this younger population. Dupilumab was generally well tolerated with an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Continuous use of several traditional systemic atopic dermati - tis (AD) treatments in pediatric patients is not recommended due to safety concerns and lack of long-term efficacy data. Children aged 6 months to 5 years with moderate-to-severe AD who had participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434, part B; parent study) were enrolled in an open-label extension (OLE) study (NCT02612454). Patients received subcutaneous dup - ilumab every 4 weeks (200 mg for children weighing 5 to <15 kg; 300 mg for 15 to <30 kg). Topical AD treatments were allowed. Relative to the parent study baseline, mean percentage changes (± standard error) in Eczema Area and Severity Index score were −41.6 (±4.6) and −54.0 (±3.2) at OLE baseline, −74.5 (±3.7) and −81.7 (±1.8) at week 16, and −85.6 (±3.5) and −86.4 (±2.2) at week 52 in the 200 and 300 mg dupilumab groups, respectively. The number of patients (%) achieving an Investigator’s Global Assessment score of 0/1 increased from OLE baseline (6/61 [9.8%] and 15/116 [12.9%]) to week 16 (22/58 [37.9%] and 35/115 [30.4%]), and at week 52 (16/34 [47.1%] and 18/54 [33.3%]) in the 200 and 300 mg dupilumab groups, respectively. The overall safety of dupilumab treatment administered for up to 1 year was consistent with the known dupilumab safety profile. Dupilumab treatment for 1 year provides sustained improvement in signs of AD in patients aged 6 months to 5 years with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

There are limited approved systemic treatment options for children with atopic dermatitis (AD). Dupilumab is now approved in the United States for patients 6 months and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies. European Medicines Agency is evaluating the use of dupilumab in children aged 6 months through 5 years with severe AD only. To report the efficacy and safety of dupilumab in the subgroup of children aged 6 months to 5 years with severe AD (IGA score=4) at baseline in the LIBERTY AD PRESCHOOL trial (NCT03346434 part B). Patients aged 6 months to 5 years with inadequately controlled moderate-to-severe AD were enrolled in LIBERTY AD PRESCHOOL (part B), a randomized, double-blind placebo-controlled phase 3 study. Patients were randomized to either dupilumab 200/300 mg every 4 weeks (200 mg if baseline weight 5 to <15 kg, 300 mg if 15 to <30 kg) or placebo for 16 weeks. All patients initiated standardized treatment with low-potency topical corticosteroids (TCS) from day –14. This analysis reports efficacy and quality-of-life endpoints including a 75% reduction from baseline in the Eczema Area and Severity Index (EASI-75), Peak-Pruritus Numerical Rating Scale (PP-NRS), Children’s Dermatology Life Quality Index (CDLQI, for children aged 4 to <6 years), and Infant’s Dermatitis Quality Of Life (IDQOL, for children <4 years) in children with severe AD. Of the total trial population of 162 patients with moderate-to-severe AD, 125 patients with severe AD at baseline were randomized: 63 to the dupilumab+TCS treatment group and 62 to the placebo+TCS treatment group. Baseline demographics were similar. Mean (SD) baseline disease characteristics were also similar between the dupilumab and placebo groups: EASI (38.8 [13.7] vs. 35.4 [12]), body surface area (63.1% [21] vs. 58.9% [21.4]), weekly average PP-NRS (7.6 [1.4] vs. 7.6 [1.6]), CDLQI (17.5 [5.5] vs. 17.8 [6.4]) and IDQOL (18.4 [5.1] vs. 17.4 [5.4]). Dupilumab treatment resulted in a rapid and significant increase in the proportion of patients achieving EASI-75 compared with placebo treatment by week 4 (27% vs. 4.8%; P=0.0009). By week 16, this improvement was further increased compared with the placebo group (46% vs. 7%; P<0.0001). At week 16, dupilumab-treated patients had a significantly greater percent reduction from baseline in PP-NRS compared with the placebo group (LS mean (SE)–41.8 [5.4] vs. 0.5 [5.4]; P<0.0001). Dupilumab also resulted in significant improvement in quality-of-life outcomes compared with placebo (LS mean [SE]) change from baseline to week 16 in CDLQI (−9.1 [1.1] vs. −2.6 [1.2]; P<0.0001); IDQOL (−9.1 [1.3] vs. −0.6 [1.1]; P<0.0001). Treatment-emergent adverse events (TEAEs) were reported in 42 (66.7%) patients in the dupilumab group and 45 (73.8%) patients in the placebo group. Most TEAEs were mild to moderate and deemed unrelated to the study drug by the investigator. The most common TEAE was atopic dermatitis in both the dupilumab group (10 [15.9%]) and placebo group (16 [26.2%]). Additionally, TEAEs in the conjunctivitis cluster were reported by 4 (6.4%) patients in the dupilumab group and none in the placebo group. In the placebo group, 3 (4.9%) serious adverse events were reported. No dupilumab-related adverse events were serious or led to treatment discontinuation. Dupilumab significantly improved AD signs, symptoms, and quality of life in children aged 6 months to 5 years with severe AD. The safety profile was consistent with that previously seen in adults, adolescents, and children aged>6 years of age. [ABSTRACT FROM AUTHOR]

Abstract Staphylococcus aureus infection is a major burden for individuals with moderate-to-severe atopic dermatitis and a known inducer of disease exacerbation. This increased susceptibility to staphylococcal infections has been attributed to abnormalities in the innate immune system of atopic dermatitis (AD) skin, including deficits in barrier proteins and lipids, and a muted response in generating antimicrobial peptides, all of which is further impaired by the activation of Th2 and Th22 immune pathways, which characterizes AD. Skewing of the immune response with a reduced Th1:Th2 ratio and increased adherence of bacteria to AD skin are also thought to contribute. Bacterial species diversity is reduced with flares, concomitant with increases in S. aureus and sometimes clinical infection, which has recently been linked to the finding that commensal bacteria produce anti– S. aureus factors that contribute to the endogenous response. S. aureus produces several virulence factors affecting the skin barrier and immune system, including promoting Th2 cell activation. Best practices for the management of staphylococcal infections include systemic antibiotics, initiation of antiseptics (particularly dilute bleach baths), and sometimes periodic intranasal mupirocin. Newer evidence suggests the possibility that treatment of the skin with commensal bacterial species could also reduce S. aureus growth and increase diversity. [ABSTRACT FROM AUTHOR]

Abstract: CHILD syndrome (Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects) is a rare X-linked dominant ichthyotic disorder. CHILD syndrome results from loss of function mutations in the NSDHL gene, which leads to inhibition of cholesterol synthesis and accumulation of toxic metabolic intermediates in affected tissues. The CHILD syndrome skin is characterized by plaques topped by waxy scales and a variety of developmental defects in extracutaneous tissues, particularly limb hypoplasia or aplasia. Strikingly, these alterations are commonly segregated to either the right or left side of the body midline with little to no manifestations on the ipsilateral side. By understanding the underlying disease mechanism of CHILD syndrome, a pathogenesis-based therapy has been developed that successfully reverses the CHILD syndrome skin phenotype and has potential applications to the treatment of other ichthyoses. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. [Copyright &y& Elsevier]

Linking phenotypic patterns of melanocytic neoplasia to specific gene mutations allows more precise predicting of clinical behavior and response to targeted therapy. In this issue, Kinsler et al. provide evidence that multiple congenital nevi with central nervous system lesions are likely exclusively the result of mosaic mutations in NRAS. We discuss the link between mosaic NRAS mutations, cellular senescence, and clinical phenotype in these nevi. [ABSTRACT FROM AUTHOR]

Identification of the underlying genetic, cellular, and biochemical basis of lipid metabolic disorders provides an opportunity to deploy corrective, mechanism-targeted, topical therapy. We assessed this therapeutic approach in two patients with Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects (CHILD) syndrome, an X-linked dominant disorder of distal cholesterol metabolism. On the basis of the putative pathogenic role of both pathway-product deficiency of cholesterol and accumulation of toxic metabolic intermediates, we assessed the efficacy of combined therapy with lovastatin and cholesterol. We also evaluated the basis for the poorly understood, unique lateralization of the cutaneous and bone malformations of CHILD syndrome by analyzing gene activation in abnormal and unaffected skin. Ultrastructural analysis of affected skin showed evidence of both cholesterol depletion and toxic metabolic accumulation. Topical treatment with lovastatin/cholesterol (but not cholesterol alone) virtually cleared skin lesions by 3 months, accompanied by histological and ultrastructural normalization of epidermal structure and lipid secretion. The unusual lateralization of abnormalities in CHILD syndrome reflects selective clearance of keratinocytes and fibroblasts that express the mutant allele from the unaffected side. These findings validate pathogenesis-based therapy that provides the deficient end product and prevents accumulation of toxic metabolites, an approach of potential utility for other syndromic lipid metabolic disorders. [ABSTRACT FROM AUTHOR]

Abstract: Background: Psychostimulants remain the most-used medications for attention-deficit/hyperactivity disorder (ADHD). The methylphenidate transdermal system (MTS) is the first stimulant patch dosage formulation to be approved by the US Food and Drug Administration for the treatment of the symptoms of ADHD in children aged 6 to 12 years. The MTS patch is approved to be applied once daily to the hip and worn for 9 hours. While cutaneous reactions may occur with any formulation of medication, they are more likely with transdermal administration. Objective: The purpose of this commentary was to describe the types of cutaneous reactions that have been reported with transdermal systems in general, review the cutaneous adverse events seen in clinical trials with the MTS specifically, and provide practical management suggestions for prevention and treatment of these potential cutaneous reactions. Methods: In September 2007, a group of child psychiatrists, pediatricians, developmental pediatricians, and pediatric neurologists who treat ADHD and have had experience in their practices with MTS convened to discuss cutaneous reactions in relation to its use. Information collected from this meeting and from the clinical trials database of the sponsor was reviewed by a panel of 3 dermatologic clinical experts in contact dermatitis and 1 pediatric dermatologist. The panel''s recommendations form the basis for this report. Conclusions: Mild to moderate erythema is a common cutaneous effect with MTS use, and is generally not a cause for discontinuation if seen in isolation. Irritant contact dermatitis is relatively common and can be reduced and treated by alternating patch application sites, moisturizing, gentle skin care, and application of topical corticosteroids at the previous patch sites if needed. Allergic contact dermatitis (ACD) and allergic contact urticaria are rare when MTS is worn as directed in the prescribing information. MTS should be discontinued if ACD is suspected. [Copyright &y& Elsevier]

Background: Etanercept, a soluble tumor necrosis factor receptor, has been shown to lessen disease severity in adult patients with psoriasis. We assessed the efficacy and safety of etanercept in children and adolescents with moderate-to-severe plaque psoriasis. Methods: In this 48-week study, 211 patients with psoriasis (4 to 17 years of age) were initially randomly assigned to a double-blind trial of 12 once-weekly subcutaneous injections of placebo or 0.8 mg of etanercept per kilogram of body weight (to a maximum of 50 mg), followed by 24 weeks of once-weekly open-label etanercept. At week 36, 138 patients underwent a second randomization to placebo or etanercept to investigate the effects of withdrawal and retreatment. The primary end point was 75% or greater improvement from baseline in the psoriasis area-and-severity index (PASI 75) at week 12. Secondary end points included PASI 50, PASI 90, physician's global assessment of clear or almost clear of disease, and safety assessments. Results: At week 12, 57% of patients receiving etanercept achieved PASI 75, as compared with 11% of those receiving placebo (P<0.001). A significantly higher proportion of patients in the etanercept group than in the placebo group had PASI 50 (75% vs. 23%), PASI 90 (27% vs. 7%), and a physician's global assessment of clear or almost clear (53% vs. 13%) at week 12 (P<0.001). At week 36, after 24 weeks of open-label etanercept, rates of PASI 75 were 68% and 65% for patients initially assigned to etanercept and placebo, respectively. During the withdrawal period from week 36 to week 48, response was lost by 29 of 69 patients (42%) assigned to placebo at the second randomization. Four serious adverse events (including three infections) occurred in three patients during treatment with open-label etanercept; all resolved without sequelae. Conclusions: Etanercept significantly reduced disease severity in children and adolescents with moderate-to-severe plaque psoriasis. (ClinicalTrials.gov number, NCT00078819.) N Engl J Med 2008;358:241-51. [ABSTRACT FROM AUTHOR]

Abstract: In this review, selected immunodeficiency disorders are presented in which the cutaneous signs are distinctive and contribute to the diagnosis of the condition. Among these cutaneous abnormalities are alopecia, cutaneous granulomas, cutaneous infections, atopic-like or seborrheic-like dermatitis, petechiae or purpura, silvery pigmentation, poor wound healing, and telangiectasias. Immunodeficiency should be considered in children with a history of infections that are recurrent, respond poorly to antibiotics, are of increased duration and severity, and/or result from unusual organisms. In addition to their high risk of infection, patients with immunodeficiency disorders have a risk of the development of malignancy that is 10,000 times higher than that of healthy age-matched controls. The underlying molecular basis for most genetic immunodeficiencies is now understood, allowing improved genetic counseling and prenatal diagnosis. [Copyright &y& Elsevier]

Moyamoya disease is a rare, chronic cerebrovascular occlusive disease of unknown etiology. It is characterized by progressive stenosis of the arteries of the circle of Willis leading to an abnormal capillary network and resultant ischemic strokes or cerebral hemorrhages. The association of moyamoya disease with livedo reticularis has been described in a previously reported patient with a factor V Leiden mutation, leading to hypercoagulation. We describe a girl with livedo reticularis and moyamoya disease with extensive cardiovascular malformations, but without a primary coagulopathy. [ABSTRACT FROM AUTHOR]

Mutations in keratin 1 were initially described in the classical form of bullous congenital ichthyosiform erythroderma (also known as epidermolytic hyperkeratosis). More recently the range of phenotypes associated with mutations in this gene has been extended to include annular ichthyosiform erythroderma and mild epidermolytic palmoplantar keratoderma. Here we present two novel mutations in the keratin 1 gene (KRT1): a 5′ donor splice site mutation in exon 1 (591 + 2T > A) that predicts a 22 amino acid in-frame deletion in the keratin 1 1A domain; and an in-frame deletion in exon 7 (1376del24) that predicts a foreshortened 2B coiled-coil domain of keratin 1. In each case these mutations are associated with palmoplantar keratoderma and mild ichthyosis, largely limited to the flexural areas. These mutations appear to have a less damaging effect than previously reported mis-sense mutations sited in the helix boundary motifs. This report extends the range of phenotypes associated with mutations in KRT1 . [ABSTRACT FROM AUTHOR]

Features the results of surveys conducted by the National Eczema Association for Science and Education to compare perceptions of physicians and patients about atopic dermatitis, its impact and its treatment. Physician practice and prescription patterns; Physician satisfaction about treatments; Impact of atopic dermatitis on the child's quality of life; Patient use and associated costs of over-the-counter atopic dermatitis medications.

Erythroderma, an inflammatory skin condition characterized by widespread erythema with variable degrees of exfoliation, pustulation, or vesiculobullous formation, is associated with high morbidity and mortality. Determining the underlying cause of erythroderma frequently presents a diagnostic challenge, which may contribute to the condition's relatively poor prognosis. This review covers the clinical presentation, pathophysiology, diagnosis, and treatment of erythroderma. It discusses similarities and differences among the many underlying etiologies of the condition and differences between erythrodermic and non-erythrodermic presentations of the same dermatosis. Finally, this article explores current research that may provide future tools in the diagnosis and management of erythroderma. [ABSTRACT FROM AUTHOR]

Background: While B‐cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B‐cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined. Objective: To compare the frequency of B‐cell subsets in blood of 0–5, 6–11, 12–17, and ≥18 years old patients with AD versus age‐matched controls. Methods: Flow cytometry was used to measure B‐cell subset frequencies in the blood of 27 infants, 17 children, 11 adolescents, and 31 adults with moderate‐to‐severe AD and age‐matched controls. IgD/CD27 and CD24/CD38 core gating systems and an 11‐color flow cytometry panel were used to determine frequencies of circulating B‐cell subsets. Serum total and allergen‐specific IgE (sIgEs) levels were measured using ImmunoCAP®. Results: Adolescents with AD had lower frequencies of major B‐cells subsets (p <.03). CD23 expression increased with age and was higher in AD compared to controls across all age groups (p <.04). In AD patients, multiple positive correlations were observed between IL‐17‐producing T‐cells and B‐cell subsets, most significantly non‐switched memory (NSM) B‐cells (r =.41, p =.0005). AD severity positively correlated with a list of B‐cell subsets (p <.05). IL‐9 levels gradually increased during childhood, reaching a peak in adolescence, paralleling allergen sensitization, particularly in severe AD. Principal component analysis of the aggregated environmental sIgE data showed that while controls across all ages tightly clustered together, adolescents with AD demonstrated distinct clustering patterns relative to controls. Conclusions: Multiple correlations between B‐cells and T‐cells, as well as disease severity measures, suggest a complex interplay of immune pathways in AD. Unique B‐cell signature during adolescence, with concurrent allergen sensitization and IL‐9 surge, point to a potentially wider window of opportunity to implement interventions that may prevent the progression of the atopic march. [ABSTRACT FROM AUTHOR]

Focuses on the molecular bases of palmoplantar keratodermas. Mutations in keratin 9 in the 1A domain of the gene; Keratin 1 gene mutations in a noncritical region; Findings of nonepidermolytic palmoplantar keratoderma resulting from mutations in keratin 6a and 16.